Trial Outcomes & Findings for A Long-Term Efficacy and Safety Study of Ixekizumab (LY2439821) in Participants With Active Psoriatic Arthritis (NCT NCT02584855)

NCT ID: NCT02584855

Last Updated: 2019-11-15

Results Overview

Relapse is loss of MDA response. MDA is achieved if 5 of 7 outcome measures are fulfilled:TJC ≤1;SJC ≤1;psoriasis activity \& severity index(PASI total score) ≤1 or body surface area(BSA) ≤3;participant pain VAS score of ≤15;participant global disease activity VAS score of ≤20;HAQ-DI score ≤0.5;and tender entheseal points ≤1.Participants met the randomization criteria if they had MDA for 3 consecutive months over 4 consecutive visits.Time-to relapse was calculated in weeks as follows:((Date of Relapse) - Date of first injection of randomized study treatment in period 3)+1) divided by 7.If the date of first dose is missing,the date of randomization will be used.Participants completing Period 3 will be censored at date of completion(the date of the last scheduled visit in the period).Participants without a date of completion or discontinuation for Period 3 will be censored at latest non-missing date out of the following dates:date of last dose \& date of last attended visit in Period 3.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 394 participants
• Primary outcome timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)
• Results posted on: 2019-11-15

Participant Flow

This study had four periods: Period 1: Screening period lasting from 4 to 30 days before Week 0, Period 2: Initial open-label treatment period from Week 0 up to Week 36, Period 3: randomized double-blind withdrawal period from Week 36 to week 104 (or, early termination or relapse) and Period 4: post treatment follow-up.

Participants were randomized during week 36 to week 64. The criteria for randomization in period 3 was having received ixekizumab (IXE) 80 mg Q2W for at least 6 months and meeting Coates criteria for minimal disease activity (MDA) for 3 consecutive months over 4 consecutive visits.The criteria was met anytime from 36 to 64 weeks.

Participant milestones

Measure	Ixekizumab Open Label Open-Label Treatment Period (OLTP): Starting dose of 160 milligrams (mg) ixekizumab given as two subcutaneous (SC) injections at baseline (Week 0) followed by 80 mg given as one SC injection every two weeks (Q2W) from week 2 to randomization (week 36 to 64).	IXE80Q2W Non-randomized Participants completed open label but did not meet criteria for randomization to the double-blind Withdrawal Period. Participants continued to receive 80 mg given as one SC injection every two weeks during the double-blind withdrawal period.	Ixekizumab Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)	IXE80Q2W Post-Treatment Follow-up Period Participants did not receive any study treatment during post treatment follow-up period. Post-Treatment Follow-up Period was summarized by last treatment assigned to a participant prior to entering the post-treatment follow up period.	Placebo Post-Treatment Follow-up Period Participants did not receive any study treatment during post treatment follow-up period. Placebo Post-Treatment Follow-up Period was summarized by last treatment assigned to a participant prior to entering the post-treatment follow up period.
Open-Label Treatment Period STARTED	394	0	0	0	0	0
Open-Label Treatment Period Received at Least One Dose of Study Drug	394	0	0	0	0	0
Open-Label Treatment Period Met Randomization Criteria	158	0	0	0	0	0
Open-Label Treatment Period Non-randomized	133	0	0	0	0	0
Open-Label Treatment Period COMPLETED	291	0	0	0	0	0
Open-Label Treatment Period NOT COMPLETED	103	0	0	0	0	0
Double-Blind Withdrawal Period STARTED	0	133	79	79	0	0
Double-Blind Withdrawal Period Relapsed	0	0	67	30	0	0
Double-Blind Withdrawal Period COMPLETED	0	118	77	78	0	0
Double-Blind Withdrawal Period NOT COMPLETED	0	15	2	1	0	0
Post Treatment Follow-up Period STARTED	0	0	0	0	355	12
Post Treatment Follow-up Period COMPLETED	0	0	0	0	347	12
Post Treatment Follow-up Period NOT COMPLETED	0	0	0	0	8	0

Reasons for withdrawal

Measure	Ixekizumab Open Label Open-Label Treatment Period (OLTP): Starting dose of 160 milligrams (mg) ixekizumab given as two subcutaneous (SC) injections at baseline (Week 0) followed by 80 mg given as one SC injection every two weeks (Q2W) from week 2 to randomization (week 36 to 64).	IXE80Q2W Non-randomized Participants completed open label but did not meet criteria for randomization to the double-blind Withdrawal Period. Participants continued to receive 80 mg given as one SC injection every two weeks during the double-blind withdrawal period.	Ixekizumab Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)	IXE80Q2W Post-Treatment Follow-up Period Participants did not receive any study treatment during post treatment follow-up period. Post-Treatment Follow-up Period was summarized by last treatment assigned to a participant prior to entering the post-treatment follow up period.	Placebo Post-Treatment Follow-up Period Participants did not receive any study treatment during post treatment follow-up period. Placebo Post-Treatment Follow-up Period was summarized by last treatment assigned to a participant prior to entering the post-treatment follow up period.
Open-Label Treatment Period Lack of Efficacy	61	0	0	0	0	0
Open-Label Treatment Period Withdrawal by Subject	21	0	0	0	0	0
Open-Label Treatment Period Adverse Event	14	0	0	0	0	0
Open-Label Treatment Period Death	2	0	0	0	0	0
Open-Label Treatment Period Lost to Follow-up	1	0	0	0	0	0
Open-Label Treatment Period Protocol Violation	1	0	0	0	0	0
Open-Label Treatment Period No PI Available	2	0	0	0	0	0
Open-Label Treatment Period Sponsor Decision	1	0	0	0	0	0
Double-Blind Withdrawal Period Withdrawal by Subject	0	0	2	0	0	0
Double-Blind Withdrawal Period Adverse Event	0	4	0	1	0	0
Double-Blind Withdrawal Period Lack of Efficacy	0	10	0	0	0	0
Double-Blind Withdrawal Period Declined Transfer to a Different Site	0	1	0	0	0	0
Post Treatment Follow-up Period Withdrawal by Subject	0	0	0	0	7	0
Post Treatment Follow-up Period Protocol Violation	0	0	0	0	1	0

Baseline Characteristics

A Long-Term Efficacy and Safety Study of Ixekizumab (LY2439821) in Participants With Active Psoriatic Arthritis

Baseline characteristics by cohort

Measure	Ixekizumab Open Label n=394 Participants Open-Label Treatment Period: Starting dose of 160 milligrams (mg) ixekizumab given as two subcutaneous (SC) injections at baseline (week 0) followed by 80 mg given as one SC injection every two weeks (Q2W) from week 2 to randomization (week 36 to 64).
Age, Continuous	47.4 years STANDARD_DEVIATION 11.40 • n=5 Participants
Sex: Female, Male Female	212 Participants n=5 Participants
Sex: Female, Male Male	182 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	330 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	48 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	385 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants
Region of Enrollment Czechia	90 participants n=5 Participants
Region of Enrollment Ukraine	43 participants n=5 Participants
Region of Enrollment Poland	60 participants n=5 Participants
Region of Enrollment Mexico	16 participants n=5 Participants
Region of Enrollment South Africa	26 participants n=5 Participants
Region of Enrollment United Kingdom	23 participants n=5 Participants
Region of Enrollment Slovakia	16 participants n=5 Participants
Region of Enrollment Bulgaria	20 participants n=5 Participants
Region of Enrollment Estonia	47 participants n=5 Participants
Region of Enrollment Russia	10 participants n=5 Participants
Region of Enrollment Spain	11 participants n=5 Participants

PRIMARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in randomized withdrawal Intent-to-Treat population. Censored participants were Ixekizumab = 49 and Placebo =12.

Relapse is loss of MDA response. MDA is achieved if 5 of 7 outcome measures are fulfilled:TJC ≤1;SJC ≤1;psoriasis activity & severity index(PASI total score) ≤1 or body surface area(BSA) ≤3;participant pain VAS score of ≤15;participant global disease activity VAS score of ≤20;HAQ-DI score ≤0.5;and tender entheseal points ≤1.Participants met the randomization criteria if they had MDA for 3 consecutive months over 4 consecutive visits.Time-to relapse was calculated in weeks as follows:((Date of Relapse) - Date of first injection of randomized study treatment in period 3)+1) divided by 7.If the date of first dose is missing,the date of randomization will be used.Participants completing Period 3 will be censored at date of completion(the date of the last scheduled visit in the period).Participants without a date of completion or discontinuation for Period 3 will be censored at latest non-missing date out of the following dates:date of last dose & date of last attended visit in Period 3.

Outcome measures

Measure	Ixekizumab n=79 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=79 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Relapse (No Longer Meeting Coates Criteria for Minimal Disease Activity [MDA])	NA Weeks Interval 64.29 to Median and upper confidence interval could not be estimated due to insufficient events in analysis duration.	22.29 Weeks Interval 16.14 to 28.29

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in randomized withdrawal Intent-to-Treat population.

Relapsed participants are defined as participants no longer meeting Coates criteria for MDA. MDA is achieved if 5 of 7 outcome measures are fulfilled: TJC ≤1; SJC ≤1; psoriasis activity and severity index (PASI total score) ≤1 or body surface area (BSA) ≤3; participant pain VAS score of ≤15; participant global disease activity VAS score of ≤20; HAQ-DI score ≤0.5; and tender entheseal points ≤1.

Outcome measures

Measure	Ixekizumab n=79 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=79 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Percentage of Participants Who Relapse in MDA	40.5 percentage of participants Interval 29.7 to 51.3	86.1 percentage of participants Interval 78.4 to 93.7

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in the randomized withdrawal Intent-to-Treat Population who had tender joint counts \<= 1 at time of randomization. Censored participants: Ixekizumab= 29 and Placebo= 16.

TJC is the number of tender and painful joints determined for each participant by examination of 68 joints.TJC possible values range from 0 to 68. A lower TJC indicated less number of joints with tenderness. A higher TJC indicated more joint tenderness. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy.

Loss of Response = Not Meeting less than or equal to 1 TJC. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=56 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=57 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Tender Joint Count 68 (TJC)	64.29 weeks Interval 24.14 to Upper confidence interval could not be estimated due to insufficient events in analysis duration.	22.29 weeks Interval 12.29 to 28.71

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in the randomized withdrawal Intent-to-Treat population who had swollen joint counts \<= 1 at time of randomization. Censored participants: Ixekizumab= 61 and Placebo = 40.

SJC is the number of swollen joints determined for each participant by examination of 66 joints. SJC possible values range from 0 to 66. A lower SJC indicated less joints with swelling. A higher SJC indicated more joints with swelling. Swelling was defined as palpable fluctuating synovitis of the joint.

Loss of Response = Not Meeting less than or equal to 1 SJC. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=72 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=73 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Swollen Joint Count 66 (SJC)	NA weeks Median and Confidence interval could not be estimated due to insufficient events in analysis duration.	28.71 weeks Interval 20.14 to Upper confidence interval could not be estimated due to insufficient events in analysis duration.

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in the randomized withdrawal intent-to-treat population Who had PASI \<= 1 at time of randomization. Censored participants: Ixekizumab = 64 and Placebo = 43.

The PASI is an index that combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease.

Loss of Response = Not Meeting less than or equal to 1 PASI total score. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=73 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=77 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Psoriasis Area and Severity Index (PASI)	NA weeks Median and Confidence Interval could not be estimated due to insufficient events in analysis duration.	36.00 weeks Interval 24.14 to 48.14

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in the randomized Withdrawal Intent-to-Treat Population who had BSA \<= 3% at time of randomization. Censored participants: Ixekizumab=70 and Placebo= 59.

BSA is an investigator evaluated measure, where the percentage of involvement of psoriasis on each participant's BSA is assessed. BSA was measured on a continuous scale from 0% = no involvement to 100% = full involvement, where 1% corresponded to the size of the participant's handprint including the palm, fingers, and thumb. Loss of Response = Not meeting less than or equal to 3% BSA.

Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=73 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=78 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: BSA	NA weeks Median and Confidence Interval could not be estimated due to insufficient events in analysis duration.	NA weeks Interval 36.0 to Confidence Interval could not be estimated due to insufficient events in analysis duration.

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in the randomized withdrawal Intent-to-Treat Population who had Pain VAS \<= 15 at time of randomization. Censored participants: Ixekizumab=42 and Placebo= 7.

The pain VAS is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two endpoints whereby the respondent places a mark on the line to indicate his or her response The scale ranges from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Loss of Response = Not Meeting less than or equal to 15 Pain VAS. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=72 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=68 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Pain Visual Analog Scale (VAS) Score	NA weeks Interval 36.14 to Confidence Interval could not be estimated due to insufficient events in analysis duration.	16.14 weeks Interval 12.14 to 22.71

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in the randomized withdrawal Intent-to-Treat population Who had PatGA VAS \<= 20 at time of randomization. Censored participants: Ixekizumab= 57 and Placebo=18.

Participants scored their overall assessment of their psoriatic arthritis (PsA) activity on a 0 to 100 mm horizontal VAS. The scale ranged from 0 (no disease activity) to 100 (extremely active disease activity). The scores were measured to the nearest millimeter from the left.

Loss of Response = Not Meeting less than or equal to 20 PatGA. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=77 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=74 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Patients Global Assessment of Disease Activity (PatGA) Visual Analog Scale (VAS) Score	NA weeks Median and Confidence Interval could not be estimated due to insufficient events in analysis duration.	20.57 weeks Interval 16.14 to 28.14

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in the randomized withdrawal Intent-to-Treat population Who had HAQ-DI \<= 0.5 at Time of randomization. Censored participants: Ixekizumab= 55 and Placebo=53.

The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.

Loss of Response = Not Meeting less than or equal to 0.5 HAQ-DI. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=69 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=68 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Health Assessment Questionnaire-Disability Index (HAQ-DI)	NA weeks Median and Confidence Interval could not be estimated due to insufficient events in analysis duration.	NA weeks Interval 48.14 to Median and Upper Confidence Interval could not be estimated due to insufficient events in analysis duration.

SECONDARY outcome

Timeframe: Double Blind Randomization through Week 104 (or Early Termination or Relapse)

Population: All participants who received at least one dose of study drug in the randomized withdrawal Intent-to-Treat Population who had tender Entheseal Point \<= 1 at time of randomization. Censored participants: Ixekizumab= 58 and Placebo= 58.

Tender entheseal points was based on the assessment of the 18 entheseal points. Loss of Response = Not Meeting less than or equal to 1 Tender Entheseal Point. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=73 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=72 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Tender Entheseal Points	NA weeks Median and Confidence Interval could not be estimated due to insufficient events in analysis duration.	NA weeks Interval 60.29 to Median and Upper Confidence Interval could not be estimated due to insufficient events in analysis duration.

SECONDARY outcome

Timeframe: Open Label Baseline through Double-Blind Randomization (Week 36 to 64)

Population: All participants who received at least one dose of study drug in initial open-label treatment period. Censored participants were 239.

Time to meeting MDA for 3 Consecutive Months Over 4 Consecutive Visits. Time to first response (in weeks) = [(date of first response - date of first injection of study treatment in the Open-Label Treatment Period)+1]/7.

Open-Label Treatment Period ended at the time when a participant was randomized so the end time was not the same for all participants. Participants were randomized only if they met randomization criteria which was at anytime from week 36 to week 64.

Outcome measures

Measure	Ixekizumab n=394 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Open-Label Treatment Period: Time to Achieve Randomization Criteria (Meeting MDA for 3 Consecutive Months Over 4 Consecutive Visits)	64.43 weeks Interval 56.14 to Upper confidence interval could not be estimated due to insufficient events in analysis duration.	—

SECONDARY outcome

Timeframe: Relapse in MDA After Double Blind Randomization through Week 104 (or Early Termination)

Population: All participants who received at least one dose of study drug and relapsed in MDA After Double Blind Randomization Until Re-Gain MDA. Censored participants were: Ixekizumab= 3 and Placebo= 3.

MDA is achieved if 5 of 7 outcome measures are fulfilled: TJC ≤1; SJC ≤1; psoriasis activity and severity index (PASI total score) ≤1 or BSA ≤3; participant pain VAS score of ≤15; participant global disease activity VAS score of ≤20; HAQ-DI score ≤0.5; and tender entheseal points ≤1. Time to first response (in weeks) = (date of first response - date of first injection of study treatment in the Relapse Period + 1)/7.

Outcome measures

Measure	Ixekizumab n=30 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=67 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Time to Re-Gain MDA Following Relapse in MDA	4.71 weeks Interval 4.14 to 8.29	4.14 weeks Interval 4.14 to 4.29

SECONDARY outcome

Timeframe: Baseline, 40 Weeks from Double Blind Randomization (Week 36 to 64)

Population: All participants who received at least one dose of study drug had a baseline and post baseline measure in the Double-Blind Withdrawal Period.

The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.Least Square (LS) mean calculated using Mixed Model Repeated Measurements (MMRM) analysis with treatment group, baseline measure, geographic region, cDMARD use, treatment week, baseline measure-by-treatment week interaction term, and treatment week-by-treatment interaction term as fixed factors.

Participants were randomized only if they met randomization criteria which was at anytime from week 36 to week 64.

Outcome measures

Measure	Ixekizumab n=51 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=22 Participants Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse)
Double-Blind Withdrawal Period: Change From Baseline in Physical Functioning Assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI)	-0.79 score on a scale Standard Error 0.06	-0.67 score on a scale Standard Error 0.06

Adverse Events

Ixekizumab Open Label

Serious events: 20 serious events

Other events: 143 other events

Deaths: 2 deaths

Ixekizumab

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

IXE80Q2W Non-randomized Population to Withdrawal Period

Serious events: 6 serious events

Other events: 37 other events

Deaths: 0 deaths

IXE80Q2W Relapse Period

Serious events: 1 serious events

Other events: 30 other events

Deaths: 0 deaths

IXE80Q2W Post-Treatment Follow-up Period

Serious events: 4 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo Post-Treatment Follow-up Period

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ixekizumab Open Label n=394 participants at risk Open-Label Treatment Period: Starting dose of 160 milligrams (mg) ixekizumab given as two subcutaneous (SC) injections at baseline (week 0) followed by 80 mg given as one SC injection every two weeks (Q2W) from week 2 to randomization (week 36 to 64).	Ixekizumab n=79 participants at risk Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=79 participants at risk Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse).	IXE80Q2W Non-randomized Population to Withdrawal Period n=133 participants at risk Participants completed open label but did not meet criteria for randomization to the double-blind Withdrawal Period. Participants continued to receive 80 mg given as one SC injection every two weeks during the double-blind withdrawal period.	IXE80Q2W Relapse Period n=97 participants at risk IXE80Q2W Relapse Period Double Blind Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse). Double Blind Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse).	IXE80Q2W Post-Treatment Follow-up Period n=355 participants at risk Participants did not receive any study treatment during post treatment follow-up period. Post-Treatment Follow-up Period was summarized by last treatment assigned to a participant prior to entering the post-treatment follow up period.	Placebo Post-Treatment Follow-up Period n=12 participants at risk Participants did not receive any study treatment during post treatment follow-up period. Placebo Post-Treatment Follow-up Period was summarized by last treatment assigned to a participant prior to entering the post-treatment follow up period.
Cardiac disorders Acute myocardial infarction	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Angina unstable	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Cardiac disorders Coronary artery disease	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Crohn's disease	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Gastritis	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Gastrointestinal necrosis	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Intestinal obstruction	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Large intestine polyp	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.3% 1/79 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Drowning	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Non-cardiac chest pain	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.28% 1/355 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Hepatobiliary disorders Cholelithiasis	0.51% 2/394 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.75% 1/133 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.28% 1/355 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Bronchitis	0.51% 2/394 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.75% 1/133 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Erysipelas	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.28% 1/355 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Pneumonia	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Sinusitis	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Urinary tract infection	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.3% 1/79 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Fall	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.75% 1/133 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Foreign body in eye	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.75% 1/133 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Meniscus injury	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.75% 1/133 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.75% 1/133 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.75% 1/133 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Thermal burn	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.0% 1/97 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Investigations Troponin increased	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.28% 1/355 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Foot deformity	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.47% 1/212 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/32 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/39 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/78 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/53 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/6 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Embolic stroke	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Transient ischaemic attack	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Vascular headache	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Reproductive system and breast disorders Endometriosis	0.00% 0/212 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.1% 1/32 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/39 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/78 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/53 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/6 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/212 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/32 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/39 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.3% 1/78 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/53 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/6 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/394 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.28% 1/355 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Skin and subcutaneous tissue disorders Angioedema	0.25% 1/394 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/133 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/97 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Other adverse events

Measure	Ixekizumab Open Label n=394 participants at risk Open-Label Treatment Period: Starting dose of 160 milligrams (mg) ixekizumab given as two subcutaneous (SC) injections at baseline (week 0) followed by 80 mg given as one SC injection every two weeks (Q2W) from week 2 to randomization (week 36 to 64).	Ixekizumab n=79 participants at risk Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse).	Placebo n=79 participants at risk Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse).	IXE80Q2W Non-randomized Population to Withdrawal Period n=133 participants at risk Participants completed open label but did not meet criteria for randomization to the double-blind Withdrawal Period. Participants continued to receive 80 mg given as one SC injection every two weeks during the double-blind withdrawal period.	IXE80Q2W Relapse Period n=97 participants at risk IXE80Q2W Relapse Period Double Blind Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse). Double Blind Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse).	IXE80Q2W Post-Treatment Follow-up Period n=355 participants at risk Participants did not receive any study treatment during post treatment follow-up period. Post-Treatment Follow-up Period was summarized by last treatment assigned to a participant prior to entering the post-treatment follow up period.	Placebo Post-Treatment Follow-up Period n=12 participants at risk Participants did not receive any study treatment during post treatment follow-up period. Placebo Post-Treatment Follow-up Period was summarized by last treatment assigned to a participant prior to entering the post-treatment follow up period.
General disorders Injection site reaction	15.0% 59/394 • Number of events 270 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.3% 1/79 • Number of events 8 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 2/133 • Number of events 20 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	7.2% 7/97 • Number of events 27 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Bronchitis	4.6% 18/394 • Number of events 23 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.1% 4/79 • Number of events 4 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.3% 1/79 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	3.8% 5/133 • Number of events 5 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.1% 4/97 • Number of events 5 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/355 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Nasopharyngitis	8.6% 34/394 • Number of events 37 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	13.9% 11/79 • Number of events 13 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.1% 4/79 • Number of events 4 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	14.3% 19/133 • Number of events 22 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	13.4% 13/97 • Number of events 17 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.56% 2/355 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Oral herpes	2.3% 9/394 • Number of events 10 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.1% 4/79 • Number of events 9 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.3% 1/79 • Number of events 3 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 2/133 • Number of events 3 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.1% 2/97 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.56% 2/355 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Upper respiratory tract infection	12.4% 49/394 • Number of events 66 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	11.4% 9/79 • Number of events 14 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.1% 4/79 • Number of events 5 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.0% 12/133 • Number of events 18 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	9.3% 9/97 • Number of events 10 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.3% 8/355 • Number of events 8 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Investigations Alanine aminotransferase increased	2.8% 11/394 • Number of events 14 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.1% 4/79 • Number of events 4 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.3% 1/79 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 2/133 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.0% 1/97 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.85% 3/355 • Number of events 3 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Investigations Aspartate aminotransferase increased	1.5% 6/394 • Number of events 8 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.1% 4/79 • Number of events 4 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.3% 1/79 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.75% 1/133 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.0% 1/97 • Number of events 3 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.56% 2/355 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/212 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.2% 2/32 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/39 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/78 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/53 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/195 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/6 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Skin and subcutaneous tissue disorders Psoriasis	0.51% 2/394 • Number of events 2 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/79 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	5.1% 4/79 • Number of events 4 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.5% 2/133 • Number of events 3 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.0% 1/97 • Number of events 1 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	1.1% 4/355 • Number of events 4 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/12 • Up To 3 Years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60